Post-transcriptional Regulation of the Arginine Transporter Cat-1 by Amino Acid Availability

The regulation of the high affinity cationic amino acid transporter (Cat-1) by amino acid availability has been studied. In C6 glioma and NRK kidney cells, cat-1 mRNA levels increased 3.8–18-fold following 2 h of amino acid starvation. The transcription rate of the cat-1 gene remained unchanged during amino acid starvation, suggesting a post-transcriptional mechanism of regulation. This mechanism was investigated by expressing a cat-1 mRNA from a tetracycline-regulated promoter. The cat-1 mRNA contained 1.9 kilobase pairs (kb) of coding sequence, 4.5 kb of 3′-untranslated region, and 80 base pairs of 5′-untranslated region. The full-length (7.9 kb) mRNA increased 5-fold in amino acid-depleted cells. However, a 3.4-kb species that results from the usage of an alternative polyadenylation site was not induced, suggesting that the cat-1 mRNA was stabilized bycis-acting RNA sequences within the 3′-UTR. Transcription and protein synthesis were required for the increase in full-lengthcat-1 mRNA level. Because omission of amino acids from the cell culture medium leads to a substantial decrease in protein synthesis, the translation of the increased cat-1 mRNA was assessed in amino acid-depleted cells. Western blot analysis demonstrated that cat-1 mRNA and protein levels changed in parallel. The increase in protein level was significantly lower than the increase in mRNA level, supporting the conclusion thatcat-1 mRNA is inefficiently translated when the supply of amino acids is limited, relative to amino acid-fed cells. Finally, y+-mediated transport of arginine in amino acid-fed and -starved cells paralleled Cat-1 protein levels. We conclude that thecat-1 gene is subject to adaptive regulation by amino acid availability. Amino acid depletion initiates molecular events that lead to increased cat-1 mRNA stability. This causes an increase in Cat-1 protein, and y+ transport once amino acids become available. The regulation of the high affinity cationic amino acid transporter (Cat-1) by amino acid availability has been studied. In C6 glioma and NRK kidney cells, cat-1 mRNA levels increased 3.8–18-fold following 2 h of amino acid starvation. The transcription rate of the cat-1 gene remained unchanged during amino acid starvation, suggesting a post-transcriptional mechanism of regulation. This mechanism was investigated by expressing a cat-1 mRNA from a tetracycline-regulated promoter. The cat-1 mRNA contained 1.9 kilobase pairs (kb) of coding sequence, 4.5 kb of 3′-untranslated region, and 80 base pairs of 5′-untranslated region. The full-length (7.9 kb) mRNA increased 5-fold in amino acid-depleted cells. However, a 3.4-kb species that results from the usage of an alternative polyadenylation site was not induced, suggesting that the cat-1 mRNA was stabilized bycis-acting RNA sequences within the 3′-UTR. Transcription and protein synthesis were required for the increase in full-lengthcat-1 mRNA level. Because omission of amino acids from the cell culture medium leads to a substantial decrease in protein synthesis, the translation of the increased cat-1 mRNA was assessed in amino acid-depleted cells. Western blot analysis demonstrated that cat-1 mRNA and protein levels changed in parallel. The increase in protein level was significantly lower than the increase in mRNA level, supporting the conclusion thatcat-1 mRNA is inefficiently translated when the supply of amino acids is limited, relative to amino acid-fed cells. Finally, y+-mediated transport of arginine in amino acid-fed and -starved cells paralleled Cat-1 protein levels. We conclude that thecat-1 gene is subject to adaptive regulation by amino acid availability. Amino acid depletion initiates molecular events that lead to increased cat-1 mRNA stability. This causes an increase in Cat-1 protein, and y+ transport once amino acids become available. asparagine synthase actinomycin D A/U-rich element base pair(s) kilobase pair(s) cationic amino acid transporter 1 cycloheximide doxycycline glyceraldehyde-3-phosphate dehydrogenase Krebs-Ringer bicarbonate buffer tetracycline untranslated region fetal bovine serum dialyzed fetal bovine serum Dulbecco's modified Eagle's medium Tris-buffered saline with Tween 20 4-morpholinepropanesulfonic acid The study of the mechanisms involved in the response of mammalian cells to amino acid availability lags behind the studies in bacteria and yeast cells. In mammalian cells, decreased amino acid availability causes substantially decreased protein synthesis (1Pain V.M. Biochimie. 1994; 76: 718-728Crossref PubMed Scopus (50) Google Scholar), as well as changes in mRNA stability and gene transcription (2Marten N.W. Burke E.J. Hayden J.M. Straus D.S. FASEB J. 1994; 8: 538-544Crossref PubMed Scopus (115) Google Scholar). Inhibition of protein synthesis involves phosphorylation of the translation factor eIF-2 (3Scorsone K.A. Panniers R. Rowlands A.G. Henshaw E.C. J. Biol. Chem. 1987; 262: 14538-14543Abstract Full PubMed Google Scholar). This results in the of with a decrease in the availability of for to the Biochimie. 1994; 76: PubMed Scopus Google Scholar). yeast cells the to for the of amino acid by the transcription of the involved in amino acid a mechanism J. Biol. Chem. 1994; Full PubMed Google Scholar). The mechanism involves the of translation of the transcription factor Biol. PubMed Google Scholar), in transcription of the amino acid J. Biol. Chem. Full Full PubMed Scopus Google Scholar). has been that mammalian cells, a mechanism to to amino acid for involved in of amino acid J. Biol. Chem. 1994; Full PubMed Google Scholar). of for synthesis is in response to amino acid R. J. Biol. Chem. Full PubMed Google Scholar), asparagine synthase Biol. PubMed Scopus Google Scholar), J. Biol. Chem. Full PubMed Google Biol. PubMed Scopus Google Scholar), and the transporter J. PubMed Scopus Google Scholar). However, the molecular mechanism of regulation of gene by amino acid availability has been for the asparagine synthase R. J. Biol. Chem. Full PubMed Google J. 1994; PubMed Scopus Google Biol. PubMed Scopus Google Scholar). The level of mRNA has been to increased by amino acid Biol. PubMed Scopus Google Scholar). This increase is by an increase in gene transcription Biol. PubMed Scopus Google and an increase in mRNA stability Biol. PubMed Scopus Google Scholar). in mRNA stability gene in mammalian cells PubMed Scopus Google Scholar). The level of an mRNA is a of rate of synthesis and rate of Amino acid depletion has been to increase the stability of the mRNA Biol. PubMed Scopus Google Scholar). We that of the cationic amino acid transporter is subject to adaptive regulation by amino acid availability in cells by a post-transcriptional mechanism of regulation J. Biol. Chem. Full Full PubMed Scopus Google Scholar). The level increased in cells of amino acids and to levels when cells were to amino medium J. Biol. Chem. Full Full PubMed Scopus Google Scholar). protein synthesis is decreased during amino acid translated (1Pain V.M. Biochimie. 1994; 76: 718-728Crossref PubMed Scopus (50) Google Scholar). increased cat-1 mRNA levels in increased protein levels in cells. the mRNA for protein synthesis once amino acid levels to In the mechanism by amino acid causes an of cat-1 that amino acid depletion causes mRNA in C6 glioma and NRK kidney cells in to the cells J. Biol. Chem. Full Full PubMed Scopus Google Scholar). that the mechanism of mRNA not regulation of increased mRNA in amino cells is for the This to by the with sequences in the of thecat-1 mRNA in amino acid-depleted cells. Finally, that increased cat-1 mRNA stability results in increased Cat-1 protein and increased cationic amino acid The transport of cationic amino acids mammalian cells is by y+ J. Biol. Chem. Full PubMed Google Scholar). been that in affinity for J. Biol. 1994; PubMed Google J. Biol. Chem. Full Full Scopus Google J. Biol. Chem. Full Full Scopus Google Scholar). The of in a amino acid for J. Biol. 1994; PubMed Google Scholar). The is the of the y+ transporter that has been to by amino acid availability J. Biol. Chem. Full Full PubMed Scopus Google Scholar). and were from was from bovine serum was from was from and were from C6 and NRK cells were in Amino acid-fed cells were in cells were amino acid-depleted by culture in Krebs-Ringer bicarbonate buffer was an to amino acids of the cat-1 J. 1994; PubMed Google Scholar). The has with the of the was to the of the to to The contained of of The of was with and of the was were and were the The following were to the and the PubMed Scopus Google with the PubMed Scopus Google Scholar), the gene and the gene PubMed Scopus Google Scholar), and Biol. PubMed Scopus Google a The full-length cat-1 is Biol. PubMed Scopus Google Scholar), suggesting an cat-1 However, in the the of the cat-1 mRNA is as to with that the the of the cat-1 mRNA J. 1994; PubMed Google Scholar). the the the cat-1 J. J. Biol. Chem. Full Full PubMed Scopus Google was from and the site of the by The was by a of the of thecat-1 J. J. Biol. Chem. Full Full PubMed Scopus Google the site of was with C6 cells the J. Scholar). cells were in and were for to for The and were in The following were to the in a of the cat-1 J. J. Biol. Chem. Full Full PubMed Scopus Google a within the of thecat-1 a glyceraldehyde-3-phosphate dehydrogenase J. J. Biol. Chem. Full Full PubMed Scopus Google a of the J. 1994; PubMed Scopus Google a of the J. J. Biol. Chem. Full Full PubMed Scopus Google a J. J. Biol. Chem. Full Full PubMed Scopus Google a from PubMed Scopus Google a of the PubMed Scopus Google a the PubMed Scopus (50) Google Scholar). for blot analysis were by with in the a from The of the was to were for RNA analysis J. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). culture cells were The were The was a of and for the was in 1 and by the of of and The was in and were of of RNA were in for and a and RNA was and with the in for were in and and the the was by the the of The was with and RNA was the following the by the was the were from cells as J. Biol. Chem. Full Full PubMed Scopus Google Scholar). were in saline and cells for were in and for were by for The was in the buffer and were in and were were by the following were to of the of and of was for and the was by the of and of This was for of buffer 20 of 2 and of yeast was The were for with 1 of with and with Finally, the and RNA was in of The RNA from was and to 2 of were for h in 1 of bovine serum and The were with for 1 h and to were to the of the and were by a the The of transcription of the in amino acid-fed and amino acid-depleted cells was the of that transcription of in cells, the of was than a gene and The relative transcription rate was as the of the the of were for to that the were within the of the and the C6 and NRK cells were in a of and for h J. PubMed Scopus Google were by the cells for 1 h the in 2 the transport the cells were for in was by the cells in and for The cells were with to and in were for and to protein analysis the were for was in the of y+ transport was as of of were a to to were with in 2 1 1 and were in in by for was by cells in 20 1 and in an for The was for The was for 1 The was in the and The protein of the was by the protein of protein were in buffer and a The was for 2 h 20 the the were in Tween 20 Tris-buffered were with the for 2 h and in for were for 1 h with the with in were for in Cat-1 and were by the The were to The were and a PubMed Scopus Google Scholar). cat-1 gene results in of a mRNA species of kb and a of kb J. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). The from alternative polyadenylation within the J. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). We that the levels of increased when cells of amino acids J. Biol. Chem. Full Full PubMed Scopus Google Scholar). regulation is a the of amino acid depletion the of the cat-1 in C6 glioma and NRK kidney cell was studied. The cat-1 gene is in cell in amino as from the of the and 3.4-kb and In cell amino acid depletion an of mRNA In NRK cells, the level of the mRNA increased in 2 a in and h and In C6 cells, the mRNA levels h and remained the of the and increase in the level of the 3.4-kb mRNA was The increase was for C6 and for NRK cells. a for regulation of gene by amino acid the levels of mRNA J. 1994; PubMed Scopus Google Scholar), is to by amino acid depletion Biol. PubMed Scopus Google J. 1994; PubMed Scopus Google Scholar). the mRNA was increased to the cat-1 mRNA The levels of the mRNA for and RNA were J. Biol. Chem. Full Full PubMed Scopus Google Scholar), the level of the mRNA decreased and h of amino acid and and the level of the RNA not 2 The of the cat-1 mRNA to increased mRNA stability to increased transcription of thecat-1 We the of amino acid depletion the transcription rate of the cat-1 gene The transcription rate of the remained the during the h of amino acid depletion in C6 and NRK cells not in with that of the cat-1 mRNA in amino acid-depleted cells is to a post-transcriptional mechanism of regulation J. Biol. Chem. Full Full PubMed Scopus Google Scholar). The transcription of to by amino acid J. 1994; PubMed Scopus Google and Biol. PubMed Scopus Google Scholar), were in The transcription rate not and the gene was Because the transcription rate of the cat-1 gene was not by amino acid transcription and protein synthesis required for mRNA protein synthesis is substantially in amino acid-depleted cells, a of to translated (1Pain V.M. Biochimie. 1994; 76: 718-728Crossref PubMed Scopus (50) Google Scholar). C6 and NRK cells were with during in amino mRNA in cell The of was by an increase in the level of mRNA is by Google Scholar). We conclude that transcription and protein synthesis required for of during amino acid the transcription rate of the cat-1 gene not in amino acid-depleted cells when with cells. The that cat-1 mRNA in amino acid-depleted cells that transcription of thecat-1 gene is during amino acid The of the mRNA in amino acid-fed cells has been to J. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). the level of the mRNA in C6 cells with for h is lower than the level in amino acid-fed cells Because regulation is not the level of that a factor is involved in the cat-1 mRNA in amino acid-depleted cells. This is by the that of the cat-1 mRNA in amino acid-depleted cells is to protein synthesis of cells with during the h of amino acid depletion results in a mRNA level to amino acid-fed cells that amino acid depletion cat-1 gene by the the levels of a mRNA from a promoter. gene was by the to a promoter. The contained 80 of the transcription site by 80 of the the coding region, and of the J. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). of the in cells in of of and from the of alternative polyadenylation within the cat-1 80 of the C6 cells were with with a that the tetracycline-regulated the and the of the cell and were for The cell results from We the of amino acid the level of the mRNA in cells. were with the tetracycline for h were in the medium was changed to amino medium in the of RNA was h of and the is for the mRNA This with the and 3.4-kb The of increased following of amino acid-fed cells with and that of the the regulation by cells were to amino acid-depleted was a increase in the level of the 2 h of the level of mRNA increased 5-fold cells in amino medium and remained the of the The level of the mRNA a increase when cells were with amino medium This increase was to the of an that has been for R. J. Biol. Chem. 1994; Full PubMed Google Scholar). The 5-fold increase of the mRNA in amino acid-depleted cells has been the increase of mRNA in amino acid-fed cells. In to the of the mRNA in amino acid-depleted cells, the 3.4-kb mRNA was not changed by amino acid depletion of cells 2 and The blot was with a for the This was a region of the that was not contained in the in the cat-1 mRNA was not by was by amino acid following the as the Because the transcription rate of is not by amino acid conclude that the increase in mRNA level is by of the the mRNA was not by amino acid conclude that the region that is in the not in the 3.4-kb mRNA sequences involved in the of thecat-1 mRNA in amino acid-depleted cells. a of the that the is stabilized by amino acid the of amino acid depletion the level of mRNA of In cells were with for h in amino The cells were to medium for in the of amino acids was that transcription of the gene when cells were to to a decrease in mRNA level. was that amino acid depletion the the decrease in the in amino acid-fed than in amino cells. The in the mRNA level in cells to base when cells were to medium in amino medium the level remained when cells were to medium amino acids This conclusion was by an for the RNA the in the of the mRNA was in amino acid-depleted cells to medium than in cells and This to the that of from the medium not transcription of gene transcription in amino the mRNA is in an increase in the mRNA level for of transcription following of is in and amino acid-fed cells in for h were to for The mRNA with a of with a the level to decrease However, an of the mRNA not the that the of the cat-1 mRNA is not by the of cells with and is during the h of culture in amino medium is that mRNA was in the in the was We that a in the level of cat-1 mRNA to the of the dialyzed of mRNA level in amino acid-fed cells. cells were in was changed to for h by culture in medium for the blot analysis of RNA from cells was and levels of mRNA level as the from the In to conclusion that of thecat-1 mRNA is in amino acid-depleted cells, the of the cat-1 mRNA was in amino acid-fed amino acid-depleted C6 cells with Cat-1 mRNA levels were assessed in cells with for than h is well that of mRNA from cells with in cat-1 mRNA with a of in amino acid-fed cells. In to the cat-1 mRNA in amino acid-depleted cells, cells were of amino acids for h and with for an h in the in and the level of cat-1 mRNA not in cells during the h of suggesting an mRNA than In to that the cells remained during the thecat-1 mRNA level was assessed in cells in amino medium for the level of cat-1 mRNA in cells was to that in cells for h 1 and In to the of the of mRNA was the of mRNA was in amino acid-depleted and cells The in and a the of cat-1 mRNA in amino acid-fed and cells In amino acid-fed cells the is the in cells is We conclude that of cat-1 mRNA is by amino acid The the in amino acid-depleted cells with sequences within the and not within the coding region of the cat-1 in increased stability. This conclusion is from the that the mRNA is not stabilized in amino acid-depleted cells The 3.4-kb mRNA the coding region and of 3′-UTR. the of a gene that contained to kb of the of the coding region of the cat-1 the in was cells was in the level of mRNA amino acid-fed and cells the of the of the in the of cat-1 mRNA in amino acid-depleted cells. the in in of the protein in amino acid-depleted cells, Cat-1 protein levels were the Cat-1 protein been by the in studies an a the of Western blot analysis was cell from the cell a of the cat-1 gene J. J.M. PubMed Scopus Google Scholar), in with from C6 cells. a of protein 80 were in C6 cells not in the cell of of the Cat-1 protein as has been for PubMed Scopus Google Scholar). The of the was demonstrated by Western in the of the the of the protein Western blot analysis was to the mRNA in amino acid-depleted cells leads to Cat-1 protein Because protein synthesis is significantly decreased in cells, an increase in Cat-1 protein that the cat-1 mRNA is translated the amino acid supply is from the of J. PubMed Scopus Google Scholar). In is demonstrated that Cat-1 protein increased by h of amino acid and remained for the of the In a with the in the level of the cat-1 mRNA was assessed in C6 cells of amino acids of of the C6 2 and protein levels that the cat-1 mRNA is not translated in amino acid-depleted cells when with amino acid-fed cells. However, the cat-1 mRNA translated than in amino acid-depleted cells, translation is significantly (1Pain V.M. Biochimie. 1994; 76: 718-728Crossref PubMed Scopus (50) Google Scholar). The increase in the Cat-1 protein level was in The level of thecat-1 mRNA was in h in not the of the Cat-1 protein with a protein to by amino acid starvation, a Western blot of cell from the in was with an J. 1994; PubMed Scopus Google Scholar), was in amino acid-depleted cells following the as mRNA 2 This is to that with Cat-1 protein, with the that the protein and mRNA to conclude that the the is translated in cells the of amino acids is protein the changes mRNA and protein by amino acid depletion in a in transport the of by C6 and NRK cells. Because y+ amino acid the of amino transport is in amino acid-depleted cells. This results from a of amino acids in the the to the transport in amino acid-fed and cells, cells were in the medium 2 for 1 h to amino acid is a for y+ transport In in amino acid-depleted C6 and NRK cells, with the by and in with results not J. Biol. Chem. Full Full PubMed Scopus Google Scholar). Because to transport were to the level of y+ in amino acid-fed and cells. of arginine in NRK and C6 cells that amino acid depletion in a of transport In cell amino acid depletion a increase in transport the in amino acid-fed cells results that the increased cat-1 mRNA in amino acid-depleted cells is translated in the that in the of cationic amino The of molecular events to increased arginine transport in amino cells was Amino acid cat-1 mRNA levels by in the cell The that regulation the post-transcriptional level, the of amino acid depletion the transcription rate is We that amino acid depletion mRNA stability. The post-transcriptional regulation is not a response to cat-1 mRNA levels not sequences of that increase stability in response to and been within the coding J. PubMed Scopus Google Scholar), the Full PubMed Scopus Google Scholar). studies of a gene in C6 cells that sequences within the of the cat-1 mRNA involved in and were from from the of alternative polyadenylation of the mRNA was not by amino acid depletion a 5-fold increase in This that the mRNA sequences for that the mRNA sequences involved in increased mRNA stability in the of the is not in the 3.4-kb mRNA J. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). The mRNA sequences and that involved in the cat-1 mRNA not is in amino acid-depleted cells, the of the cat-1 mRNA is a protein factor is that the Because the of the cat-1 mRNA in C6 amino acid-fed cells is J. J. Biol. Chem. Full Full PubMed Scopus Google and the sequences to J. J. Biol. Chem. Full Full PubMed Scopus Google Scholar), is that A/U-rich sequences within the J. J. Biol. Chem. Full Full PubMed Scopus Google involved in is well that in the of Full PubMed Scopus Google R. Full PubMed Scopus Google Scholar). The of the cat-1 mRNA of the and the J. J. Biol. Chem. Full Full PubMed Scopus Google Scholar). has been that the of is by a of as Biol. PubMed Scopus Google Scholar). and R. PubMed Scopus Google demonstrated that the is involved in the of A/U-rich involves a of with translation factor and protein R. PubMed Scopus Google Scholar). of by and of the in of by and of mRNA R. PubMed Scopus Google Scholar). of in the of cat-1 mRNA in amino acid-depleted cells. However, of the of cat-1 mRNA in amino acid-depleted cells, cat-1 mRNA stability. alternative mechanism that the in amino acid-depleted cells is the synthesis of a protein that to the mRNA This of regulation has been for regulation of PubMed Scopus Google and J. PubMed Scopus Google Scholar). has been that a to an within the of of the mRNA Biol. PubMed Scopus Google Scholar). The of the not the 3.4-kb cat-1 mRNA and a of the not is that a protein in amino acid-depleted cells thecat-1 mRNA by a of the This is for in the regulation mRNA in amino acid-depleted cells. of mRNA has been to to the mechanism of mRNA is not well is that of translation of the PubMed Scopus Google Scholar). However, increased stability of by of translation of the Biol. PubMed Scopus Google Scholar). In studies that protein synthesis is required for cat-1 mRNA in amino acid-depleted cells. This thatcat-1 mRNA stability in cells is with to translated that translation is required for the synthesis of a protein factor that the the that of the in amino acid-depleted cells not to Because the increase in the level of the Cat-1 protein was lower than the increase in the level of mRNA conclude that the cat-1 mRNA is inefficiently translated in amino acid-depleted cells, relative to amino acid-fed cells. of the Cat-1 protein was in amino acid-depleted C6 cells and cells the gene not The that the mRNA not translated in amino acid-depleted cells. of the to translated to the of the is that translation during amino acid depletion is required for the synthesis of a protein that cat-1 mRNA stability. This conclusion is by the that of amino acid-depleted cells with a protein synthesis leads to a decrease mRNA to levels not is by the that levels of cat-1 not increase during the 2 h of amino acid The of 2 h required for the synthesis of the protein that mRNA stability. alternative is that the 2 h is required to the that changes in gene in amino acid-depleted cells. The from the studies in is mRNA level in amino acid-depleted cells the mRNA is not to translated Cat-1 is well (1Pain V.M. Biochimie. 1994; 76: 718-728Crossref PubMed Scopus (50) Google Scholar), protein synthesis significantly in amino acid-depleted cells. to the of cat-1 mRNA is inefficiently translated in amino acid-depleted cells, relative to amino acid-fed cells. This that the increased level for the translation and the level of Cat-1 protein during the of The that Cat-1 protein for as as h in amino acid-depleted cells that is a protein that synthesis alternative for the of the Cat-1 protein in amino acid-depleted cells is that results from translation of the the is not is the of the protein with the of the studies the of translation of the in amino acid-depleted cells. The level of y+ arginine transport in amino acid-depleted cells is to the as Cat-1 We that y+ arginine transport is in amino acid-depleted cells J. Biol. Chem. Full Full PubMed Scopus Google Scholar). We in that is in amino acid-depleted NRK and C6 cells. We conclude that of the cat-1 mRNA in amino acid-depleted cells to Cat-1 protein level and cationic amino acid transport during depletion and once amino acids become available. of the for cat-1 and regulation Biol. PubMed Scopus Google Biol. PubMed Scopus Google Scholar). of the gene by amino acid depletion has been to the and post-transcriptional levels Biol. PubMed Scopus Google Biol. PubMed Scopus Google Scholar). the transcription rate of the gene in amino acid-fed and -starved cells not by 2 studies of that the is subject to regulation in amino acid-depleted cells Biol. PubMed Scopus Google Scholar). is thatcat-1 gene transcription is by amino acid was not by In of is the that a increase in the level of the mRNA was in amino acid-depleted cells J. Biol. Chem. Full Full PubMed Scopus Google Scholar). The by amino acid depletion changes in gene in mammalian cells not has been that increased levels of the regulation of gene by transcription mRNA stability J. Biol. Chem. 1994; Full PubMed Google Scholar). events the synthesis of the of that as transcription mRNA In of a to of gene is the that is in amino acid-depleted cells to a regulation of by a of J. Biol. Chem. Full Full PubMed Scopus Google Scholar). The molecular events that gene in response to changes in the supply been in and lower J. Biol. Chem. 1994; Full PubMed Google Scholar). cells mechanisms to to availability J. Biol. Chem. 1994; Full PubMed Google Scholar). We that of response involves the of gene by a mechanism that involves post-transcriptional of the studies transporter in response to amino acid starvation. the regulation of amino acid transporter by amino acid availability increase of regulation of amino acid transport in and cells during of protein